Martelli A, Allavena A, Ghia M, Robbiano L, Brambilla G
Institute of Pharmacology, University of Genoa, Italy.
Toxicol Appl Pharmacol. 1993 May;120(1):114-9. doi: 10.1006/taap.1993.1093.
1,3-Dichloropropene (DCP), a widely used soil fumigant previously found to be carcinogenic in both mice and rats, was evaluated for its cytotoxic and genotoxic effects in cultured rodent and human cells. A reduction of cell viability that was dependent on the dose and the length of treatment was observed with the trypan blue and the neutral red assay in both V79 cells and rat hepatocytes exposed to DCP concentrations ranging from 0.18 to 5.6 mM. In the absence of a metabolic activation system, a dose-dependent frequency of DNA single-strand breaks, that were only partially repaired within 24 hr, was revealed by the alkaline elution technique in V79 cells exposed to subtoxic DCP concentrations. The genotoxicity of DCP was confirmed by the results obtained in metabolically competent primary cultures of both rat and human hepatocytes which displayed similar dose-related amounts of DNA fragmentation and DNA repair synthesis, and showed, in comparison to metabolically deficient V79 cells, a somewhat greater sensitivity to the cytotoxic and DNA-damaging effects of DCP. The increase in the frequency of DNA breaks observed in rat hepatocytes after GSH depletion confirms the role of this tripeptide in DCP detoxification; its reduction in hepatocytes simultaneously exposed to metyrapone is consistent with a cytochrome P450-dependent biotransformation of DCP to more toxic metabolites.
1,3 - 二氯丙烯（DCP）是一种广泛使用的土壤熏蒸剂，先前已发现它对小鼠和大鼠均具有致癌性，本文对其在培养的啮齿动物细胞和人类细胞中的细胞毒性和遗传毒性作用进行了评估。在锥虫蓝和中性红试验中，观察到暴露于浓度范围为0.18至5.6 mM的DCP的V79细胞和大鼠肝细胞的细胞活力降低，且这种降低取决于剂量和处理时间。在缺乏代谢活化系统的情况下，碱性洗脱技术显示，暴露于亚毒性DCP浓度的V79细胞中，DNA单链断裂频率呈剂量依赖性，且这些断裂在24小时内仅部分得到修复。大鼠和人类肝细胞的代谢活性原代培养物所获得的结果证实了DCP的遗传毒性，这些培养物显示出类似的剂量相关的DNA片段化和DNA修复合成量，并且与代谢缺陷的V79细胞相比，对DCP的细胞毒性和DNA损伤作用表现出更高的敏感性。谷胱甘肽耗竭后大鼠肝细胞中观察到的DNA断裂频率增加证实了这种三肽在DCP解毒中的作用；在同时暴露于美替拉酮的肝细胞中其含量降低，这与DCP经细胞色素P450依赖性生物转化为毒性更强的代谢产物一致。
